Dendritic cell presentation of antigens from apoptotic cells in a proinflammatory context - Role of opsonizing anti-beta(2)-glycoprotein I antibodies

Objective. To verify whether opsonization of apoptotic cells skews the outc ome of apoptotic cell antigen presentation by dendritic cells (DCs). Methods. RMA cells, which were engineered with a mutant ovalbumin (OVA) pro tein and were devoid of the leader secretory sequence (OVA-RMA), underwent ultraviolet irradiation to induce apoptosis, Binding of anti-beta(2)-glycop rotein I antibodies (anti-beta(2)GPI) and phagocytosis of apoptotic cells w ere assessed by flow cytometry and confocal microscopy. Presentation of pro cessing antigens and major histocompatibility complex (MHC) class II-restri cted or MHC class I-restricted antigens was assessed using OVA-specific T c ell hybridomas. Results, Anti-beta(2)GPI facilitated presentation of epitopes from internal ized apoptotic cells to MHC class II-restricted, but not to class I-restric ted, T lymphocytes. DCs challenged with supernatants of apoptotic cells did not activate OVA-specific T cells, making it unlikely that anti-beta(2)GPI complexed with antigen released from dying cells plays a role in antigen p resentation. DCs challenged with low numbers of anti-beta(2)GPI-opsonized a poptotic cells secreted interleukin-1 beta (IL-1 beta), tumor necrosis fact or ct, and IL-10 in an autocrine/paracrine manner. Conclusion. Opsonization influences the outcome of the disposal of low numb ers of apoptotic cells by DCs, This implies that soluble factors bound to a poptotic cells modulate their immunogenicity.